A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure. The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and <<1% of all pancreatic cancer) is approximately 35%. Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic tumors that represent the only radiographically identifiable precursor lesion of pancreatic cancer and represent approximately 20% - 30% of pancreatic malignancy. Current laboratory, endoscopic, and imaging technologies are unable to distinguish between IPMN that is at low-risk (low-grade dysplasia) or high-risk (high-grade dysplasia) of becoming malignant. We have recently identified differentially expressed proteins (IL-1b, IL-5, IL-8, MUC-2, MUC-4) in the cyst fluid of patients with high-risk IPMN. We hypothesize that antibody bead array of cyst fluid can be utilized as a diagnostic tool to identify patients with pre-malignant cysts of the pancreas (IPMN) that are at high risk for progressing to malignancy. In this proposal we will incorporate the differentially expressed proteins noted above into an antibody bead array that we have used in cyst fluid analysis for the discrimination of benign pancreatic cysts. Antibody bead array analysis will be performed on cyst fluid from patients with pathologically proven (resected) low-risk (low and moderate grade dysplasia) and high-risk (high-grade dysplasia) IPMN. Differential protein expression will be compared between low-risk and high-risk IPMN to evaluate for additional markers of dysplasia. Sample classification will be used to develop a model for predicting high-grade dysplasia. This model, developed from operatively obtained samples, will then be evaluated on samples obtained endoscopically (endoscopic ultrasound aspiration). Development of a preoperative test to discriminate between low-risk and high-risk IPMN would allow patients with high-risk lesions to be resected prior to the development of an essentially incurable disease, and enable patients with low-risk lesions to avoid operation and spare them the physical, emotional, and financial costs of pancreatectomy. PUBLIC HEALTH RELEVANCE: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are radiographically identifiable cystic precursor lesions of pancreatic cancer that evolve from low-grade dysplasia to high-grade dysplasia to carcinoma. Recently we have identified promising protein biomarkers (MUC-2, MUC-4, IL-1b, IL-5, IL- 8) from the cyst fluid of patients with IPMN that are differentially expressed in low-risk and high-risk lesions. In this proposal we plan to incorporate these biomarkers into an antibody bead array that we have previously utilized in cyst fluid analysis and assess whether a cyst fluid assay can be developed to identify patients with IPMN who are at high-risk of developing pancreatic cancer.